IDENTIFICATION OF DRUG-RESISTANT MYELOID LEUKEMIC-CELLS BY MEASUREMENT OF DNA CONTENT, NUCLEAR-AREA, AND DETECTION OF P-GLYCOPROTEIN

BACKGROUND, This study was designed to evaluate the significance of an euploidy DNA ploidy, nuclear area, and expression of P-glycoprotein (P -GP) in differentiating drug-resistant myeloid leukemic cells (DRMLC) from drug-sensitive myeloid leukemic cells. METHODS. Bone marrow aspir ates from 28 myeloid leukemic patients were fixed in 95% ethanol solut ion and stained using the Papanicolaou method. The nuclear area and DN A content were measured. An immunohistochemical study was performed us ing monoclonal antibody (JSB-1) directed against P-GP. RESULTS. Leukem ic cell morphology changed once or twice after the diagnosis of acute myeloid leukemia (AML), blastic crisis (BC) of chronic myeloid leukemi a, or chronic neutrophilic leukemia. DRMLC showed severe atypia and we re morphologically distinguishable from normal myeloblasts, promyelocy tes, and drug-sensitive leukemic cells at the diagnosis of AML or BC. The mean nuclear index (NI) and DNA index (DI) of DRMLC were significa ntly larger than those of drug-sensitive leukemic cells of AML or BC. The frequency of aneuploidy and P-GP expression was 9.1% and 4.5%, res pectively, at the diagnosis of AML or BC, and 92.8% and 28.5%, respect ively, for resistant disease. The incidence of heterogeneity in DNA pl oidy was 86.3%. CONCLUSIONS. DI and NI values larger than 1.2 and the expression of P-GP are significant indications of DRMLC. (C) 1996 Amer ican Cancer Society.